Frequency of functional exonic single-nucleotide polymorphisms and haplotype distribution in the SLCO1B1 gene across genetic ancestry groups in the Qatari population.

Organic anion transporting polypeptides (OATP), which are encoded by SLCO genes, participate in the hepatic elimination of drugs and xenobiotics. SLCO1B1 is an important pharmacogenomic gene (encoding OATP1B1) associated with response to the uptake of endogenous compounds, such as statin and bilirubin. Ethnicity of the patient modulates the response to these drugs; the frequency and haplotype data for SLCO1B1 genetic variants in the Arab population is lacking. Therefore, we determined the frequencies of two well-characterized SLCO1B1 single nucleotide polymorphisms (SNP) and haplotypes that affect the OATP1B1 drugs transportation activity in Qatari population. Genotyping data for two SLCO1B1 SNPs (c.388A > G, c.521 T > C) were extracted from whole exome data of 1050 Qatari individuals, who were divided into three ancestry groups, namely Bedouins, Persians/South Asians, and Africans. By way of using Fisher's exact and Chi-square tests, we evaluated the differences in minor allele frequency (MAF) of the two functional SNPs and haplotype frequencies (HF) among the three ancestry groups. The OATP1B1 phenotypes were assigned according to their function by following the guidelines from the Clinical Pharmacogenetics Implementation Consortium for SLCO1B1 and Simvastatin-Induced Myopathy.The MAF of SLCO1B1:c.388A > G was higher compared to that of SLCO1B1:c.521 T > C in the study cohort. It was significantly high in the African ancestry group compared with the other two groups, whereas SLCO1B1:c.521 T > C was significantly low in the African ancestry group compared with the other two groups. The SLCO1B1 *15 haplotype had the highest HF, followed by *1b, *1a, and *5. Only the SLCO1B1 *5 haplotype showed no significant difference in frequency across the three ancestry groups. Furthermore, we observed that the OATP1B1 normal function phenotype accounted for 58% of the Qatari individuals, the intermediate function phenotype accounted for 35% with significant differences across the ancestry groups, and the low function phenotype accounted for 6% of the total Qatari individuals with a higher trend observed in the Bedouin group.The results indicate that the phenotype frequencies of the OATP1B1 intermediate and low function in the Qatari population appear at the higher end of the frequency range seen worldwide. Thus, a pharmacogenetic screening program for SLCO1B1 variants may be necessary for the Qatari population.

Distribution of HLA-B Alleles and Haplotypes in Qatari: Recommendation for Establishing Pharmacogenomic Markers Screening for Drug Hypersensitivity.

Human leukocyte antigen (HLA) proteins are present at the cellular surface of antigen-presenting cells and play a crucial role in the adaptive immune response. Class I genes, specifically certain HLA-B alleles, are associated with adverse drug reactions (ADRs) and are used as pharmacogenetic markers. Although ADRs are a common causes of hospitalization and mortality, the data on the prevalence of HLA-B pharmacogenetics markers in Arab countries are scarce. In this study, we investigated the frequencies of major HLA-B pharmacogenomics markers in the Qatari population. Next-generation sequencing data from 1,098 Qatari individuals were employed for HLA-B typing using HLA-HD version 1.4.0 and IPD-IMGT/HLA database. In addition, HLA-B pharmacogenetics markers were obtained from the HLA Adverse Drug Reaction Database. In total, 469 major HLA-B pharmacogenetic markers were identified, with HLA-B*51:01 being the most frequent pharmacogenetic marker (26.67%) in the Qatari population. Moreover, HLA-B*51:01 is associated with phenytoin- and clindamycin-induced ADRs. The second most frequent pharmacogenetic marker was the HLA-B*58:01 allele (6.56%), which is associated with allopurinol-induced ADRs. The third most frequent pharmacogenetic marker was the HLA-B*44:03 allele, which is associated with phenytoin-induced ADRs. The establishment of a pharmacogenetics screening program in Qatar for cost effective interventions aimed at preventing drug-induced hypersensitivity can be aided by the highly prevalent HLA-B pharmacogenetic markers detected here.

Carbon Monoxide Poisoning in Kuwait: A Five-Year, Retrospective, Epidemiological Study.

BACKGROUND: Carbon monoxide (CO) poisoning is a major public health concern and a common cause of death worldwide. However, to our knowledge, no studies have been conducted on CO poisoning exposure and mortality in Kuwait. OBJECTIVES: Using epidemiological and forensic data analysis, we investigated the prevalence and characteristics of CO poisoning-associated deaths in Kuwait over five years (2014-2018), using official police data. METHODS: The Forensic Toxicology Laboratory analyzed 203 blood specimens of deceased individuals for potential CO poisoning during the study period. We obtained demographic information of the deceased and other information regarding the source of the CO, the type of death and the seasonal and geographical distribution of fatalities. The percentage of carboxyhemoglobin (COHb%) was assessed using a CO-oximeter. RESULTS: CO poisoning was confirmed in ~29% (59 cases) of the analyzed specimens, of which CO poisoning was accidental in the majority of cases (~95%) and homicidal in the remaining of cases (~5%), with no reported suicides. The five-year cumulative mean of COHb% in the blood specimens of the 59 confirmed cases was ~63%. Most of the deceased were males (~68%). The mean age of male and female victims per year were similar (~23-38 years). Fatalities were more common (~44%) during the winter (December-February). Uncontrolled home fires and coal stoves contributed to the primary sources of CO poisoning at 61% and 22%, respectively. RECOMMENDATIONS: Based on our findings, we propose that the local government should mandate the installation of smoke alarms and CO detectors in residential settings and endorse health education, informing the local population about the causes of fire and potential for CO poisoning, with an emphasis on prevention. Practical measures that can be applied include proper installation and regular maintenance of home-heating appliances and appropriate ventilation. The present study could greatly benefit the government in directing efforts toward decreasing CO poisoning incidents in Kuwait in the future.

Snapshot of narcotic drugs and psychoactive substances in Kuwait: analysis of illicit drugs use in Kuwait from 2015 to 2018.

BACKGROUND: The misuse of illicit substances is associated with increased morbidity and mortality; thus, substance abuse is a global health concern. The Arabian Gulf region is considered a crossing point and a consumer of illicit drugs. However, a lack of laboratory-based research has limited the scientific assessment of drug misuse in the Arabian Gulf region. Thus, an up-to-date analytical representation of the drug situation is warranted. METHODS: We investigated the type and quantity of detained narcotic drugs and psychotropic substances from 2015 to 2018, representing a population of approximately 4 million people, in addition to the number of abusers and mortality among abusers. In total, 6220 cases from the Narcotic and Psychotropic Laboratory and 17,755 cases from the Forensic Toxicology Laboratory were reviewed and analyzed. Substances were identified and documented using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. RESULTS: Cannabis, including marijuana, was the most seized substance, followed by heroin, opium, and cocaine. Amphetamines, including methamphetamine, in the form of powder or pills, were seized in larger quantities than other psychoactive substances. The most consumed substances were, in order, amphetamines (including methamphetamine), benzodiazepines, cannabis, and heroin. We identify the common drugs in postmortem specimens, according to sex, from suspected drug-related deaths. The most common single drug identified were heroin, benzodiazepines, and methamphetamine. Similarly, the multiple-drug cocktail of heroin-benzodiazepines, cannabis-benzodiazepines, and cannabis-amphetamines, were detected frequently. CONCLUSIONS: The data shows that cannabis is the leading type of illicit substance seized. Deaths resulting from benzodiazepines and heroin abuse were the highest in the single drug category, while heroin-benzodiazepines combination deaths were the highest in the multiple-drug category. Methamphetamine was the most abused illicit drug in Kuwait. These findings revealed the illicit drug abuse situation in the State of Kuwait, in a region that suffers from the scarcity of information regarding illicit substances. Thus, providing valuable information for drug enforcement, forensic analyst, health workers on national and international levels.

Identification of synthetic cannabinoids that were seized, consumed, or associated with deaths in Kuwait in 2018 using GC-MS and LC-MS-MS analysis.

Synthetic cannabinoids are gaining much popularity worldwide. Although the death rate associated with their use is rising, these drugs are the largest and fastest growing class of novel psychoactive substances. Despite increased concerns regarding adverse effects stemming from the use of synthetic cannabinoids, there is no published data on the subject for the Gulf region or Kuwait, specifically. The current study investigates the diversity of synthetic cannabinoids in Kuwait in 2018. In total, 434 cases from the Narcotics and Psychotropic Laboratory, 70 cases from the Toxicology Laboratory, and six cases from the Forensic Medicine Department were reviewed and analyzed. Numerous synthetic cannabinoid types were identified using GC-MS and LC-MS-MS. The majority of synthetic cannabinoids were members of the indazole-3-carboxamide or indole-3-carboxamide families. Members from the indazole-3-carboxamide family identified in Kuwait were 5F-ADB, FUB-AMB, ADB-FUBINACA, AB-FUBINACA, 5F-ADB-PINACA, 5F-AKB-48, 5Cl-AKB-48, MDMB-FUBINACA, 5F-AB-PINACA, APINACA, and AB-PINACA whereas MDMB-CHMICA, 5F-MDMB-PICA, ADB-BICA, and MMB-CHMICA belonged to the indole-3-carboxamide family. In addition, members of other families were identified, including CBL2201 and UR-144, which belonged to indole-3-carboxylate and cyclopropylindole families, respectively. The most common synthetic cannabinoids were 5F-ADB, FUB-AMB, and 5Cl-AKB-48. Various mixes of two, three, or four types of synthetic cannabinoids were identified, and mixtures of synthetic cannabinoids with other illicit drugs were also present. Our findings show that in Kuwait, the most common mix of synthetic cannabinoids is FUB-AMB with 5F-ADB. These two types were mixed, either together or individually, with methamphetamine, tramadol, heroin, Δ9THC, and ketamine. Most importantly, our results reveal the synthetic cannabinoid types that were associated with six reported deaths.